Quack G, Hesselink M, Danysz W, Spanagel R
Department of Pharmacology, Merz & Co. GmbH & Co., Frankfurt, Federal Republic of Germany.
J Neural Transm Suppl. 1995;46:97-105.
Amantadine and memantine are in clinical use for the treatment of neurodegenerative diseases such as M. Parkinson and dementia syndrome. In order to contribute to the understanding of the interaction of these uncompetitive NMDA-antagonists with the dopaminergic system in the striatum, the pharmacokinetics and the effects of amantadine and memantine on the dopaminergic system were examined in a microdialysis study in anaesthetized rats. Both substances achieved extracellular fluid concentrations in the striatum known to block NMDA receptors, supporting the assumption that NMDA receptor antagonism is their primary mechanism of action. Both, memantine, and to a lesser degree, amantadine induce a modest dopamine overflow not paralleled by HVA or DOPAC. The small increase in dopamine overflow cannot add substantially to the drugs' action and may be generated indirectly via their NMDA-antagonistic properties.
金刚烷胺和美金刚在临床上用于治疗帕金森病和痴呆综合征等神经退行性疾病。为了有助于理解这些非竞争性N-甲基-D-天冬氨酸（NMDA）拮抗剂与纹状体中多巴胺能系统的相互作用，在一项对麻醉大鼠的微透析研究中，检测了金刚烷胺和美金刚的药代动力学及其对多巴胺能系统的影响。两种物质在纹状体中均达到了已知可阻断NMDA受体的细胞外液浓度，这支持了NMDA受体拮抗作用是其主要作用机制的假设。美金刚以及程度较轻的金刚烷胺均会引起适度的多巴胺溢出，而高香草酸（HVA）或3,4-二羟基苯乙酸（DOPAC）并未出现相应变化。多巴胺溢出的小幅增加对药物作用的贡献不大，可能是通过其NMDA拮抗特性间接产生的。
